Discussion about concerns that some dodgy treatments get promoted by patients to patients.

[alex3619]

It's basically a crossover when you try something stop then reintroduce it.

https://en.wikipedia.org/wiki/Crossover_study

Actually even the reference refutes this would be a crossover study.

A crossover clinical trial is a repeated measures design in which each patient is randomly assigned to a sequence of treatments, including at least two treatments (of which one "treatment" may be a standard treatment or a placebo).

A typical crossover study in papers I have read have two treatments, and at half time, sometimes with a short washout period, every patient (who was randomly assigned to the original group) is assigned to the opposite group. That way every patient has both treatments, but at different times.

 

[alex3619]

I don't have that problem so don't say we.

Please explain. How do you definitively find out the cause unless you are using theory driven assumptions? How do you empirically identify the cause? People have been struggling with this for decades.

 

[JalapenoLuv]

Please explain. How do you definitively find out the cause unless you are using theory driven assumptions? How do you empirically identify the cause? People have been struggling with this for decades.

My work has been to test theory by using agents that target molecular apoptosis pathways and note the response. So if you think that pathway X has blocked apoptosis and you give agent A with the result being neuropathy and eventual healing it strongly supports the theory provided the agent doesn't do this in normals and in people with autoimmune disease (AD). I've already been screened for AD and it has been ruled out.

 

[alex3619]

My work has been to test theory by using agents that target molecular apoptosis pathways and note the response. So if you think that pathway X has blocked apoptosis and you give agent A with the result being neuropathy and eventual healing it strongly supports the theory provided the agent doesn't do this in normals and in people with autoimmune disease (AD). I've already been screened for AD and it has been ruled out.

AD cannot be ruled out. Only known AD can be ruled out. There are secondary markers though, the absence of which can suggest no AD. How is your sIL2r for example? There are lots more, but they escape me at the moment.

Healing from an agent only suggests the theory is right. You have to demonstrate mechanisms, and the mechanisms are active. Then move to large scale dbRCTs. Even then it can be wrong.

You may also be using theory driven assumptions, eg:

So if you think that pathway X has blocked apoptosis and you give agent A ...

Let us suppose agent B is working, and agent D, and agent H. The other agents don't work. Why don't they work? Why do these specific agents work (presuming this is accurate for now)? Many agents have multiple chemical effects, and variable response in different organs. How do you know which effect is working?

For example, when I was investigating quaifenesin there were lots of responders. Yet the model relied on assumptions about alterations to intracellular and mitochondrial phosphate. These were implausible. So an effect had to be via another pathway, or accidental, or something. If they involved phosphate then they did so via another mechanism.

Such alternative mechanisms can also include things we have not discovered yet.

As I pointed out in my blog (link given earlier in this thread) even the success of an agent does not prove the theory behind the agent is correct.

Lets take Rituximab. Clearly it works very successfully in about 6% of patients. We do not know why ... yet. It also fails completely in about 30% of patients. Again we do not know why.

Quoting an earlier comment of yours:

The main problem is that many of the supplements (alpha lipoic acid, resversatrol, knotweed, milk thistle, quercitin, green tea and tobacco) being pushed by the gurus as helpful are actually harmful because they are anti-apoptosis and suppress the reactions; so people think they feel better because there are fewer free radicals but it really is just that they suppressed their immune system.

Let us take resveratrol/knotweed. Anyone thinking that resveratrol has as its primary effect an antioxidant effect is not following the science. The primary mechanism is via indirectly raising cAMP, therefore shifting the Ca++/cAMP axis. This profoundly alters intracellular signalling. The argument against resveratrol could be made on that basis though ... its a blunt instrument.

Or take alpha lipoic acid. In addition to being a critical antioxidant, its an essential factor in glucose metabolism.

I am less sure about milk thistle, green tea or quercetin. Tobacco I think is just a bad idea.

There is also chance. Things change, sometimes outside of our control. So if a change occurs, how do you know its not just some unanticipated or unmeasured factor? That is why science requires it be duplicated many times in many subjects. This is in hope that random factors can be ruled out. However even then there can be systematic unanticipated factors that skew an entire study. This could even be from something as simple as using the wrong assay.

One final point:

...it strongly supports the theory provided...

This suggests that there may be risk of confirmation bias. Hypotheses have to be robustly tested, in addition to having supporting data. N=1 is not sufficient. It is not clear how many people these factors have been tested on from your comment.

Please note this particular thread is relevant to experimental design, and reliability of information. A thread on a given hypothesis should probably be separate.

 

[MeSci]

I don't have that problem so don't say we.

I said 'we tend to', meaning a majority of us, not all. Sorry if that wasn't clear.

 

[MeSci]

Let us take resveratrol/knotweed. Anyone thinking that resveratrol has as its primary effect an antioxidant effect is not following the science. The primary mechanism is via indirectly raising cAMP, therefore shifting the Ca++/cAMP axis. This profoundly alters intracellular signalling. The argument against resveratrol could be made on that basis though ... its a blunt instrument.

A hazard of using knotweed-derived resveratrol is that many such supplements also contain emodin, which can harm the gut and cause vomiting and diarrhoea. It may not be mentioned on the label, but IMO it should be. I fell foul of this undeclared ingredient.

I presume that grape-derived resveratrol doesn't contain emodin.

 

[xchocoholic]

Why do some people use terms such as promoted, advertised or pushed when discussing what posters have written ?

I just noticed that the title of this thread uses the term promoted. I saw someone say diet was being pushed the other day. I forget where I saw someone using the term advertised.

Tx .. x

 

[MeSci]

My work has been to test theory by using agents that target molecular apoptosis pathways and note the response. So if you think that pathway X has blocked apoptosis and you give agent A with the result being neuropathy and eventual healing it strongly supports the theory provided the agent doesn't do this in normals and in people with autoimmune disease (AD).

Do you know of any successful treatments in which neuropathy is a stage towards recovery? This is a genuine question which I ask for two reasons:

1. Neuropathy can be an indication of something seriously wrong.
2. I developed something similar to neuropathy (numb hands) some months ago and am hoping that it is not a sign of something seriously wrong!

 

[alex3619]

Do you know of any successful treatments in which neuropathy is a stage towards recovery? This is a genuine question which I ask for two reasons:

1. Neuropathy can be an indication of something seriously wrong.
2. I developed something similar to neuropathy (numb hands) some months ago and am hoping that it is not a sign of something seriously wrong!

I was still thinking about this @MeSci, you beat me to it. In part I was wondering if this was a typo.

 

[JalapenoLuv]

Do you know of any successful treatments in which neuropathy is a stage towards recovery? This is a genuine question which I ask for two reasons:

1. Neuropathy can be an indication of something seriously wrong.
2. I developed something similar to neuropathy (numb hands) some months ago and am hoping that it is not a sign of something seriously wrong!

Yes. It is still in testing but early results follow the pattern I described above. That's what nerve apoptosis does, kill the infected nerves and let the remaining ones take over function. I can't list it here but I'm planning on opening up the treatment for pilot testing later.

 

[alex3619]

Yes. It is still in testing but early results follow the pattern I described above. That's what nerve apoptosis does, kill the infected nerves and let the remaining ones take over function. I can't list it here but I'm planning on opening up the treatment for pilot testing later.

The downside of this is what I said before, and may make this treatment untenable ... extensive nerve death may mean permanent extensive disability, or even death. It depends on what is infected, how pervasively, etc. There would need to be some really good science behind this before it would ever be approved as a treatment. That is presuming, of course, that it works as claimed.

 

[MeSci]

Yes. It is still in testing but early results follow the pattern I described above. That's what nerve apoptosis does, kill the infected nerves and let the remaining ones take over function. I can't list it here but I'm planning on opening up the treatment for pilot testing later.

What if all the nerves are infected? Or all the nerves serving a particular function? You could end up paralysed or dead.

 

[MeSci]

The downside of this is what I said before, and may make this treatment untenable ... extensive nerve death may mean permanent extensive disability, or even death. It depends on what is infected, how pervasively, etc. There would need to be some really good science behind this before it would ever be approved as a treatment. That is presuming, of course, that it works as claimed.

Great minds think alike!

 

[JalapenoLuv]

Luckily the whole process seems to take 1-3 months so someone could stop and not get to that point. The worst thing would be that they would be stuck with chronic CFS.

 

[MeSci]

Luckily the whole process seems to take 1-3 months so someone could stop and not get to that point. The worst thing would be that they would be stuck with chronic CFS.

How would you know when to stop?

 

[golden]

Why do some people use terms such as promoted, advertised or pushed when discussing what posters have written ?

I just noticed that the title of this thread uses the term promoted. I saw someone say diet was being pushed the other day. I forget where I saw someone using the term advertised.

Tx .. x

Trialling something is good. Gaining individual feedback of how something effected me is useful (and can never be accomplished by any gold standard trials - particularly being in the female form and not Living in a Lab.

Having good unbiased observations is even better. Sharing this is great.

 

[JalapenoLuv]

How would you know when to stop?

Still working on that, not really a big issue.

 

[alex3619]

Trialling something is good. Gaining individual feedback of how something effected me is useful (and can never be accomplished by any gold standard trials - particularly being in the female form and not Living in a Lab.

Having good unbiased observations is even better. Sharing this is great.

My lemon rule comes to mind:

22. Most treatments for ME are lemons, they don't suit everyone - but you often wont know if it suits you until you suck it and see. If you see a soured look on my face you will know why.

 

[JalapenoLuv]

My lemon rule comes to mind:

22. Most treatments for ME are lemons, they don't suit everyone - but you often wont know if it suits you until you suck it and see. If you see a soured look on my face you will know why.

ME is a tough disease to treat. In working on the bartonella spp. ebv type I ran into four different molecular pathways that the organisms were interfering with. Also complicating matters was the fact that many popular antiviral and antioxidant boosting supplements (knotweed, resversatrol, quercitin, green tea, alpha lipoic acid and tobacco) actually make the disease worse by blocking apoptosis over the same pathways. So if you take them you feel better but they make you worse because they mask symptoms.

 

[alex3619]

ME is a tough disease to treat. In working on the bartonella spp. ebv type I ran into four different molecular pathways that the organisms were interfering with. Also complicating matters was the fact that many popular antiviral and antioxidant boosting supplements (knotweed, resversatrol, quercitin, green tea, alpha lipoic acid and tobacco) actually make the disease worse by blocking apoptosis over the same pathways. So if you take them you feel better but they make you worse because they mask symptoms.

All claims. In keeping with the theme of this thread, where is the evidence?

I am not saying you are wrong. I am saying you have not provided sufficient evidence. I have seen so many hypotheses over the years. Most had some suggestive evidence. Then people took that as proof. There is a reason science has so many requirements to demonstrate that hypotheses are robust.

If I were on an ethics committee, reviewing any study along the lines claimed so far, I would reach for the safety studies. No safety studies, no approval.

People have gone to prison for murder (over laetrile) for small experiments in which people died. Safety is paramount.

If something causes neuropathy its very likely that the FDA, for example, will never approve it. Though this depends on what is causing the neuropathy. If its a temporary suspension of nerve capacity, then they might. If nerves actually die in numbers, then its very unlikely they will ever give approval.

After safety studies, I would reach for studies on outcome measures. How was recovery measured? What were the objective markers? Only after those would I look at subjective outcomes, to see if they differed in implication from the objective ones. (On this point CBT/GET fails - there is a clear mismatch between objective and subjective outcomes.)

If a treatment worked, and safety was acceptable, and likely responders and non-responders could be identified, then I would consider approval. However, that does not mean I would presume the theory is correct.

For example, Rituximab can induce full remission, and historically it was first used to treat lymphoma (RA came later I think), but I would not want to presume that its mechanism in ME is essentially the same as in lymphoma. I would want to see the mechanism tested, and pathways mapped, and then tested in light of the new understanding, and so on.

Just as a side point, I have a suspicion that neuropathy is a common long term consequence of ME, and that too much may lead to multiple organ failure, a common cause of death in us. It is also becoming clearer that many of us have comorbid fibromyalgia, and that this might in fact be a neuropathic disease.

Bold hypotheses are good. They have to be coupled with cautious and robust science though.